The Importance of Making a Genetic Diagnosis of Diabetes

Abstract

Monogenic diabetes accounts for approximately 1 to 2% of diabetes, although it is often mistakenly diagnosed as either type 1 or type 2 diabetes, depending on patient age and mode of presentation. Knowing the genetic etiology of diabetes allows better prediction of disease progression, screening of family members and genetic counselling regarding transmission risk. This review focuses on 2 forms of monogenic diabetes: maturity-onset diabetes of the young (MODY) and permanent neonatal diabetes mellitus (PNDM). Recent research has shown that these forms of diabetes require specific therapy, often with dramatic impact for the patient. Within MODY, the different subtypes can essentially be divided into 2 distinct groups: glucokinase MODY and transcription factor MODY, distinguished by characteristic phenotypic features and pattern on oral glucose tolerance testing. Glucokinase MODY requires no treatment, while transcription factor MODY (i.e. hepatocyte nuclear factor - 1alpha) requires low-dose sulfonylurea therapy and PNDM (caused by Kir6.2 mutation) requires high-dose sulfonylurea therapy.